Ibuprofen (2-(4-isobutylphenyl) propionic acid) has one chiral center, thus there are two enantiomers, S (+)-ibuprofen (dexibuprofen) and R (−)-ibuprofen, also known as (S+)-ibuprofen and (R−)-ibuprofen. The racemic form consisting of equal amounts of S(+)-ibuprofen and R(−)-ibuprofen is exclusively used in the currently available commercial preparations, as well as the water soluble salts of ibuprofen such as lysinate, arginate, sodium, potassium etc are also used. Racemic ibuprofen has relatively high melting point (about 78° C.), while both stereoisomer's of ibuprofen, S (+)-ibuprofen and R (−)-ibuprofen, melt at 52° C. to 54° C. All the different forms of ibuprofen are poorly soluble in water Notably, the S (+) form alone appears to be responsible for the anti-inflammatory activity, not the R (−) form (S. Adams et al., Curr. Med. Res. Opin., 3, 552 (1975); S. Adams et al., J. Pharm. Pharmaco., 28, 256-257 (1976)).
U.S. Pat. No. 5,093,133 discloses hydroalcoholic gel formulations of (S)-ibuprofen as an effective vehicle for percutaneous delivery of (S+)-ibuprofen through the skin. In this patent, the hydroalcoholic gel of (S+)-ibuprofen is prepared by using 40 to 60% of alcohol; 0-20% of a non-volatile solvent; 2.0 to 5.0% of gelling agents; sufficient base, to adjust the pH to between 3.5 to 6.0; and water.
U.S. Pat. No. 5,767,161 discloses a pharmaceutical composition in the form of cream, foam or stick containing 2.5-10% by weight (S)-2-(4-isobutylphenyl)propionic acid, 20-30% by weight ethanol and 5-50% by weight propylene glycol, the ratio of ethanol to propylene glycol is 0.6-1 to 4:1. This patent also reports an increase in cutaneous permeation of the active ingredient with respect to those obtained by known topical pharmaceutical compositions containing an equivalent or higher amount of Ibuprofen.
U.S. Pat. No. 6,368,618 discloses a novel two phase liquid topical formulation for delivery of S(+)-ibuprofen, which is characterized by enhanced transdermal absorption and efficacy. In this patent two phase system consist of an aqueous and oil phases, the oil phase contains a relatively high concentration of the S (+)-ibuprofen making it directly available for partitioning into the stratum corneum without the rate-limiting diffusion process from the inert oil phase as in a conventional cream.
U.S. Pat. No. 5,696,165 discloses phaimaceutical compositions for oral, rectal or topical administration containing (S)-Ibuprofen sodium salt as an active ingredient. This patent reports that the S(−)sodium 2-(4-isobutylphenyl) propionate has advantage over S(+) 2-(4-isobutylphenyl)propionate for preparing pharmaceutical compositions containing water and additional formulation advantage is that S(−)sodium 2-(4-isobutylphenyl)propionate will resist esterification with excipients which contain a hydroxyl group for example mono-, di-, tri- or polyhydric alcohols.
As disclosed in the prior arts dexibuprofen is formulated into topical formulations either using high amount of alcohol or using a two phase system to enhance the transdermal absorption and efficacy.
Thus, there is a constant need to formulate topical formulation of dexibuprofen which can be prepared by simple manufacturing process and should also provide an effective transdermal penetration.